434 research outputs found
Defective protein prenylation is a diagnostic biomarker of mevalonate kinase deficiency
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177329.pdf (Publisher’s version ) (Open Access
Long RNA sequencing and ribosome profiling of inflamed beta-cells reveal an extensive translatome landscape
Type 1 diabetes (T1D) is an autoimmune disease characterized by autoreactive T cell-mediated destruction of the insulin-producing pancreatic beta -cells. Increasing evidence suggest that the beta -cells themselves contribute to their own destruction by generating neoantigens through the production of aberrant or modified proteins that escape central tolerance. We recently demonstrated that ribosomal infidelity amplified by stress could lead to the generation of neoantigens in human beta -cells, emphasizing the participation of nonconventional translation events in autoimmunity, as occurring in cancer or virus-infected tissues. Using a transcriptome-wide profiling approach to map translation initiation start sites in human beta -cells under standard and inflammatory conditions, we identify a completely new set of polypeptides derived from noncanonical start sites and translation initiation within long noncoding RNA. Our data underline the extreme diversity of the beta -cell translatome and may reveal new functional biomarkers for beta -cell distress, disease prediction and progression, and therapeutic intervention in T1D.Molecular Epidemiolog
Accretion and ejection in black-hole X-ray transients
Aims: We summarize the current observational picture of the outbursts of
black-hole X-ray transients (BHTs), based on the evolution traced in a
hardness-luminosity diagram (HLD), and we offer a physical interpretation.
Methods: The basic ingredient in our interpretation is the Poynting-Robertson
Cosmic Battery (PRCB, Contopoulos & Kazanas 1998), which provides locally the
poloidal magnetic field needed for the ejection of the jet. In addition, we
make two assumptions, easily justifiable. The first is that the mass-accretion
rate to the black hole in a BHT outburst has a generic bell-shaped form. This
is guaranteed by the observational fact that all BHTs start their outburst and
end it at the quiescent state. The second assumption is that at low accretion
rates the accretion flow is geometrically thick, ADAF-like, while at high
accretion rates it is geometrically thin.
Results: Both, at the beginning and the end of an outburst, the PRCB
establishes a strong poloidal magnetic field in the ADAF-like part of the
accretion flow, and this explains naturally why a jet is always present in the
right part of the HLD. In the left part of the HLD, the accretion flow is in
the form of a thin disk, and such a disk cannot sustain a strong poloidal
magnetic filed. Thus, no jet is expected in this part of the HLD. The
counterclockwise traversal of the HLD is explained as follows: the poloidal
magnetic field in the ADAF forces the flow to remain ADAF and the source to
move upwards in the HLD rather than to turn left. Thus, the history of the
system determines the counterclockwise traversal of the HLD. As a result, no
BHT is expected to ever traverse the entire HLD curve in the clockwise
direction.
Conclusions: We offer a physical interpretation of accretion and ejection in
BHTs with only one parameter, the mass transfer rate.Comment: Accepted for publication in A&
Unbounded violation of tripartite Bell inequalities
We prove that there are tripartite quantum states (constructed from random
unitaries) that can lead to arbitrarily large violations of Bell inequalities
for dichotomic observables. As a consequence these states can withstand an
arbitrary amount of white noise before they admit a description within a local
hidden variable model. This is in sharp contrast with the bipartite case, where
all violations are bounded by Grothendieck's constant. We will discuss the
possibility of determining the Hilbert space dimension from the obtained
violation and comment on implications for communication complexity theory.
Moreover, we show that the violation obtained from generalized GHZ states is
always bounded so that, in contrast to many other contexts, GHZ states do in
this case not lead to extremal quantum correlations. The results are based on
tools from the theories of operator spaces and tensor norms which we exploit to
prove the existence of bounded but not completely bounded trilinear forms from
commutative C*-algebras.Comment: Substantial changes in the presentation to make the paper more
accessible for a non-specialized reade
An overview of jets and outflows in stellar mass black holes
In this book chapter, we will briefly review the current empirical
understanding of the relation between accretion state and and outflows in
accreting stellar mass black holes. The focus will be on the empirical
connections between X-ray states and relativistic (`radio') jets, although we
are now also able to draw accretion disc winds into the picture in a systematic
way. We will furthermore consider the latest attempts to measure/order jet
power, and to compare it to other (potentially) measurable quantities, most
importantly black hole spin.Comment: Accepted for publication in Space Science Reviews. Also to appear in
the Space Sciences Series of ISSI - The Physics of Accretion on to Black
Holes (Springer Publisher
Synthesis and DPPH scavenging assay of reserpine analogues, computational studies and in silico docking studies in AChE and BChE responsible for Alzheimer's disease
Alzheimer's disease (AD) is a fast growing neurodegenerative disorder of the central nervous system and anti-oxidants can be used to help suppress the oxidative stress caused by the free radicals that are responsible for AD. A series of selected synthetic indole derivatives were biologically evaluated to identify potent new antioxidants. Most of the evaluated compounds showed significant to modest antioxidant properties (IC50 value 399.07 140.0±50 µM). Density Functional Theory (DFT) studies were carried out on the compounds and their corresponding free radicals. Differences in the energy of the parent compounds and their corresponding free radicals provided a good justification for the trend found in their IC50 values. In silico, docking of compounds into the proteins acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), which are well known for contributing in AD disease, was also performed to predict anti-AD potential
Species abundance distributions: moving beyond single prediction theories to integration within an ecological framework
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75247/1/j.1461-0248.2007.01094.x.pd
Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET
The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR
On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection
A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)
Relationship of edge localized mode burst times with divertor flux loop signal phase in JET
A phase relationship is identified between sequential edge localized modes (ELMs) occurrence times in a set of H-mode tokamak plasmas to the voltage measured in full flux azimuthal loops in the divertor region. We focus on plasmas in the Joint European Torus where a steady H-mode is sustained over several seconds, during which ELMs are observed in the Be II emission at the divertor. The ELMs analysed arise from intrinsic ELMing, in that there is no deliberate intent to control the ELMing process by external means. We use ELM timings derived from the Be II signal to perform direct time domain analysis of the full flux loop VLD2 and VLD3 signals, which provide a high cadence global measurement proportional to the voltage induced by changes in poloidal magnetic flux. Specifically, we examine how the time interval between pairs of successive ELMs is linked to the time-evolving phase of the full flux loop signals. Each ELM produces a clear early pulse in the full flux loop signals, whose peak time is used to condition our analysis. The arrival time of the following ELM, relative to this pulse, is found to fall into one of two categories: (i) prompt ELMs, which are directly paced by the initial response seen in the flux loop signals; and (ii) all other ELMs, which occur after the initial response of the full flux loop signals has decayed in amplitude. The times at which ELMs in category (ii) occur, relative to the first ELM of the pair, are clustered at times when the instantaneous phase of the full flux loop signal is close to its value at the time of the first ELM
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